Falk Jessica A, Aune Sverre E, Kutala Vijay K, Kuppusamy Periannan, Angelos Mark G
Department of Emergency Medicine, Ohio State University, Columbus, OH, United States.
Resuscitation. 2007 Sep;74(3):508-15. doi: 10.1016/j.resuscitation.2007.01.026. Epub 2007 Apr 6.
Previous reports note an increase in both reactive oxygen species (ROS) and nitric oxide (*NO) at the onset of myocardial reperfusion. We tested the hypothesis that inhibition of *NO or ROS production at the time of reperfusion improves recovery of post-ischemic myocardial function.
Isolated rat hearts were perfused with temperature controlled (37.4 degrees C) modified Krebs Henseleit buffer solution at 85 mm Hg. Following 20 min of global ischemia, hearts were reperfused for the first 10 min with: (1) standard buffer (control), (2) buffer with a NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME), (3) buffer with superoxide dismutase (SOD) or (4) buffer with N-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite generator. Tissue O(2) and *NO were continuously measured with thin electrochemical probes embedded in the wall of the LV. ROS was measured with the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) (40 mM). LV contractile function was continuously monitored.
Recovery of LV contractile function was significantly improved in hearts initially reperfused with L-NAME and SOD and significantly depressed in hearts reperfused with SIN-1 compared with control (p<0.01, n=5-8 per group). DMPO-adduct during reperfusion (measure of ROS) was significantly decreased with SOD (p<0.001 versus L-NAME and Control, n=4 per group) and unchanged with L-NAME and SIN-1 compared with Control. With L-NAME, tissue *NO and PO(2) were significantly decreased, independent of coronary flow, during reperfusion compared with control and SIN-1.
Inhibition of O(2)*(-) or *NO at the time of reperfusion improves early reperfusion LV function and alters tissue oxygen tension. In contrast to pre-ischemic treatments, intervention to reduce peroxynitrite generation at the onset of reperfusion can effectively improve post-ischemic myocardial recovery.
既往报道指出，心肌再灌注开始时活性氧（ROS）和一氧化氮（NO）均增加。我们检验了以下假设：再灌注时抑制NO或ROS生成可改善缺血后心肌功能的恢复。
将离体大鼠心脏在85 mmHg下用温度控制在37.4℃的改良Krebs Henseleit缓冲溶液灌注。在全心缺血20分钟后，心脏在最初的10分钟再灌注期间分别使用：（1）标准缓冲液（对照），（2）含有一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯（L-NAME）的缓冲液，（3）含有超氧化物歧化酶（SOD）的缓冲液，或（4）含有过氧亚硝酸盐生成剂盐酸N-吗啉代辛二亚胺（SIN-1）的缓冲液。用嵌入左心室壁的薄电化学探头连续测量组织氧（O₂）和*NO。用自旋捕捉剂5,5-二甲基-1-吡咯啉N-氧化物（DMPO）（40 mM）测量ROS。连续监测左心室收缩功能。
与对照组相比，最初用L-NAME和SOD再灌注的心脏左心室收缩功能恢复显著改善；而用SIN-1再灌注的心脏左心室收缩功能恢复显著降低（p<0.01，每组n = 5 - 8）。再灌注期间DMPO加合物（ROS的测量指标）在用SOD时显著降低（与L-NAME和对照组相比，p<0.001，每组n = 4），与对照组相比，L-NAME和SIN-1组无变化。使用L-NAME时，与对照组和SIN-1组相比，再灌注期间组织*NO和PO₂显著降低，且与冠脉血流无关。
再灌注时抑制O₂*(-)或*NO可改善再灌注早期左心室功能并改变组织氧张力。与缺血前治疗不同，在再灌注开始时减少过氧亚硝酸盐生成的干预措施可有效改善缺血后心肌恢复。
